休克等临床重症存在血管低反应性，它严重制约休克等重症的治疗，现有机制仅局限在血管平滑肌细胞（VSMC）本身收缩系统上，没有注意细胞器和亚细胞器的作用，不能完全解释其机制。内质网应激（ERS）是真核细胞中普遍存在的一种保护性反应，过度应激会导致组织细胞损害，以前认为它主要诱导细胞凋亡，是否参与休克血管舒缩功能调控不清楚。本实验室前期研究发现脓毒性休克VSMC ERS参与了休克后血管低反应的发生，线粒体通透性转换孔（MPTP）关闭剂可减轻这种血管低反应性，推测休克后的ERS可能通过启动VSMC MPTP开放参与休克后血管低反应性的发生。椐此，本研究拟以脓毒性休克大鼠和VSMC为研究对象，研究内质网应激启动MPTP开放在休克血管低反应性中的作用，探讨内质网应激启动MPTP开放及MPTP开放调节血管反应性的分子机制，提出休克血管低反应性发生的新机制，为休克等重症的治疗提供新的靶点和调控策略。

Vascular hyporeactivity exists in many critical conditions such as severe trauma and shock, which severely restricts the treatment of these diseases. It is of significance to elucidate the mechanism for probing the effective therapeutic measures. The present mechanisms are mainly limited to the contractile system of vascular smooth muscle cell, it did not pay attention to the role of organelle and sub-organelle. Endoplasmic reticulum stress(ERS) is the protective response that presents in real nucleus cells. Its over activation will cause cell damage. Previous studies showed that ERS mainly participated in the regulation of cell apoptosis, it is not clear if ERS participated in the occurrence of vascular hyporeactivity following shock.The previous study in our Lab found that ERS in VSMC participated in the incidence of vascular hyporesponsiveness following septic shock. The close agent of mitochondrial permeability transition pore (cyclosporine A,CsA) reduced this vascular hyporesponsiveness. Therefore, we hypothesize that ERS may take part in the occurrence of shock-induced vascular hyporeactivity via initiation of MPTP opening. To test this hypothesis, we will use septic shock rats and vascular smooth muscle cells to investigate the role of ERS initiation of MPTP opening in shock-induced vascular hyporeactivity and investigate the mechanism that ERS induces MPTP opening and MPTP regulates the vascular reactivity following shock. The main objective tends to raise the new mechanism to explain the occurrence of vascular hyporeactivity, and provide the new therapeutic targets and modulation strategy for clinical critical conditions such as severe trauma and shock.